Congenital Melanotic Macule of the Tongue: Report of Two Cases and Literature Review.

BACKGROUND: Congenital melanotic macule of the tongue (CMMT) has been described as a distinct entity, despite its unknown etiology. However, the diagnosis and management of affected newborns may challenge clinicians and pediatric dentists. METHODS: We document here the clinicopathological findings of two additional cases of CMMT. A literature review of CMMT reports identified across PubMed, Web of Science, Embase, and Scopus was also conducted. RESULTS: The patients, 2- and 4 month-old Venezuelan boys, respectively, presented at birth with a single or multiple dark-brown-pigmented macule exclusively on the dorsum of the tongue. Histopathological features revealed increased melanin pigmentation in the basal epithelial layer with overlying hyperkeratosis and pigment-laden subepithelial macrophages with normal morphological appearance. Nine studies comprising 17 cases of CMMT have been described hitherto. Most cases were from the USA and France (n = 6 each). Twelve (70.6%) patients were males, eight (50%) were white, and median age was 2.7 months. CMMT presented as brownish to black, solitary or multiple pigmentations located in the right or left region of the dorsum of the tongue, ranging in size from 3.0 to 30.0 mm. CONCLUSION: An important feature for the diagnosis of CMMT is the information about the manifestation at birth and consequent proportional growth. This report intends to draw the attention of pediatricians and dentists to this apparently underdiagnosed condition for decision-making and management of affected newborns.

Melanosis neurocutánea: reporte de un caso y revisión de la literatura / Neurocutaneous melanosis. Case report and literature review

Introducción: la melanosis neurocutánea es un trastorno congénito no hereditario que se caracteriza por la asociación de nevus pigmentados múltiples o de gran tamaño y una excesiva proliferación de melanocitos en el sistema nervioso central. La incidencia es similar en ambos sexos, y se observa historia familiar de melanoma en un único caso. Presentación del caso: se trata de un neonato masculino que nace en Hospital General de Luanda en Angola, con mancha melánica gigante que se extiende desde el cuello, cara, tórax, abdomen, espalda y miembros superiores, requiere una vigilancia de las lesiones dérmicas y un control de las crisis convulsivas. Discusión: se realizaron revisiones de la literatura médica disponible sobre el tema, consultando el programa de genética Oxford, y se tomaron fotos de las características clínicas sobresalientes. Por lo general los síntomas neurológicos son de temprana aparición en la etapa neonatal o de lactante con presencia de convulsiones de difícil control, al crear un pronóstico reservado. Conclusiones: se considera importante el seguimiento del neurodesarrollo de forma multidisciplinario para intervención oportuna si fuera necesario(AU)

Introduction: neurocutaneous melanosis is a non-hereditary congenital disorder characterized by the association of multiple or large pigmented nevi and an excessive proliferation of melanocytes in the central nervous system. The incidence is similar in both sexes, and a family history of melanoma is observed in a single case. Case presentation: this is a male neonate born at the General Hospital of Luanda in Angola, with a giant melanic spot that extends from the neck, face, chest, abdomen, back and upper limbs, requires surveillance of dermal lesions and control of seizures. Discussion: reviews of the available medical literature on the subject were conducted, consulting the Oxford genetics program, and photos of outstanding clinical features were taken. Usually the neurological symptoms are of early onset in the neonatal or infant stage with the presence of seizures that are difficult to control, creating a reserved prognosis. Conclusions: it is considered important to monitor neurodevelopment in a multidisciplinary way for timely intervention if necessary(EU)

[Melanosis of adipose tissue in a 17-month-old German Fleckvieh bull (Bos taurus)]. / Melanose von Fettgewebe bei einem 17 Monate alten Stier der Rasse Deutsches Fleckvieh (Bos taurus).

At meat inspection of a 17-month-old bull (German Fleckvieh), patchy dark discoloration of various organs and tissue sites was noted that was most prominent in perirenal adipose tissue. Microscopic analysis revealed melanosis, that is a congenital melanocytic dystopia, as the underlying cause. To the best of our knowledge, this is the first case of melanosis detected in adipose tissue in cattle. We speculate that there is a possible pathogenetic link between obesity and melanosis in the animal.

A pilot study demonstrating the efficacy of transcutaneous bilirubin meters to quantitatively differentiate contusions from Congenital Dermal Melanocytosis.

OBJECTIVE: Congenital Dermal Melanocytosis (CDM) can be difficult to differentiate from contusions. The need for a prompt and accurate diagnosis is best illustrated in cases where child abuse and maltreatment is of concern. Transcutaneous bilirubin (TCB) spectrophotometry has been well established to measure bilirubin under the skin for jaundice in infants. The use of TCB spectrometry has not been used to identify or differentiate contusions from CDM. We hypothesized that bilirubin, a degradation product of hemoglobin, would be elevated in contusions but not in CDM thus demonstrating the efficacy of a novel diagnostic technique to compliment or improve on physical assessment alone. METHODS: Pilot study with thirty-seven infants and children noted to have CDM and fifty-six infants, children and adults with contusions underwent measurement of their lesion with TCB spectrometry. In each patient, the affected skin was scanned along with the adjacent unaffected native skin allowing an internal control for individual pigment variation. RESULTS: TCB measurements of CDM resulted in lower transcutaneous bilirubin values that were not significantly different from adjacent native skin pigmentation. This was in contrast to cutaneous contusions, which resulted in a higher measured value (mean 5.01 mg/dL) compared to adjacent native tissue (1.24 mg/dL) demonstrating a four-fold increase in measurement at the lesion site (P < 0.001). Direct comparison of a ΔTCB value (lesion measurement minus the adjacent tissue) demonstrated a significantly higher value in contusions compared to CDM with a mean value of 3.77 and 0.12 mg/dL, respectively (P < 0.001). CONCLUSIONS: TCB Spectrometry as a novel diagnostic technique has the potential to discern contusions from CDM and may therefore have the ability to compliment the use of physical assessment alone.

Congenital Melanocytic Nevus Syndrome: A Case Series. / Síndrome del nevus melanocítico congénito. Serie de casos.

Congenital melanocytic nevus syndrome (CMNS) is the result of an abnormal proliferation of melanocytes in the skin and central nervous system caused by progenitor-cell mutations during embryonic development. Mutations in the NRAS gene have been detected in many of these cells. We present 5 cases of giant congenital melanocytic nevus, 3 of them associated with CMNS; NRAS gene mutation was studied in these 3 patients. Until a few years ago, surgery was the treatment of choice, but the results have proved unsatisfactory because aggressive interventions do not improve cosmetic appearance and only minimally reduce the risk of malignant change. In 2013, trametinib was approved for use in advanced melanoma associated with NRAS mutations. This drug, which acts on the intracellular RAS/RAF/MEK/pERK/MAPK cascade, could be useful in pediatric patients with CMNS. A better understanding of this disease will facilitate the development of new strategies.

Giant congenital melanocytic nevi: selected aspects of diagnostics and treatment.

BACKGROUND: Treatment of giant melanocytic nevi (GMN) remains a multidisciplinary challenge. We present analysis of diagnostics, treatment, and follow- up in children with GMN to establish obligatory procedures in these patients. MATERIAL/METHODS: In 24 children with GMN, we analyzed: localization, main nevus diameter, satellite nevi, brain MRI, catecholamines concentrations in 24-h urine collection, surgery stages number, and histological examinations. The t test was used to compare catecholamines concentrations in patient subgroups. RESULTS: Nine children had "bathing trunk" nevus, 7 had main nevus on the back, 6 on head/neck, and 2 on neck/shoulder and neck/thorax. Brain MRI revealed neurocutaneous melanosis (NCM) in 7/24 children (29.2%), symptomatic in 1. Among urine catecholamines levels from 20 patients (33 samples), dopamine concentration was elevated in 28/33, noradrenaline in 15, adrenaline in 11, and vanillylmandelic acid in 4. In 6 NCM children, all catecholamines concentrations were higher than in patients without NCM (statistically insignificant). In all patients, histological examination of excised nevi revealed compound nevus, with neurofibromatic component in 15 and melanoma in 2. They remain without recurrence/metastases at 8- and 3-year-follow-up. There were 4/7 NCM patients with more than 1 follow-up MRI; in 1 a new melanin deposit was found and in 3 there was no progression. CONCLUSIONS: Early excision with histological examination speeds the diagnosis of melanoma. Brain MRI is necessary to confirm/rule-out NCM. High urine dopamine concentration in GMN children, especially with NCM, is an unpublished finding that can indicate patients with more serious neurological disease. Treatment of GMN children should be tailored individually for each case with respect to all medical/psychological aspects.

Congenital melanotic macules of the tongue. A case report and brief review of the literature.

Congenital melanotic macules of the tongue (CMMT) are a rare and benign condition that is probably underestimated. We report the case of an African infant with multiple congenital hyperpigmented macules of the tongue. To avoid a difficult-to-perform procedure such as a tongue biopsy, focused clinical monitoring was performed every 3 months for 30 months to detect significant changes. A clinical diagnosis of CMMT was made in the absence of concomitant systemic diseases using the clinical findings, the location on the tongue, the negative family history for melanoma, and the absence of drugs and toxic exposure. Clinical follow-up may be sufficient to monitor CMMT rather than performing a tongue biopsy.

Choroidal melanocytosis evaluation with enhanced depth imaging optical coherence tomography.

OBJECTIVE: To assess eyes with unilateral choroidal melanocytosis using enhanced depth imaging (EDI) optical coherence tomography (OCT). DESIGN: Retrospective, observational case series. PARTICIPANTS: Fifteen patients with unilateral choroidal melanocytosis. METHODS: Each patient was evaluated with EDI-OCT, and comparison was made of involved versus uninvolved foveal retinal and choroidal layers. MAIN OUTCOME MEASURES: Enhanced depth imaging OCT features of choroidal melanocytosis. RESULTS: The mean patient age was 28 years (median, 23 years; range, 5-76 years). There were 9 male and 6 female patients. Best-corrected visual acuity ranged from 20/20 to 20/30. All patients had subfoveal involvement with choroidal melanocytosis. Associated features included dermal (n = 6), scleral (n = 9), iris (n = 3), and palate (n = 1) melanocytosis. Spectral domain EDI-OCT revealed normal inner retina (n = 15) and normal outer retina (n = 14). The only retinal abnormality was a defect in both the myoid zone and the ellipsoid junction (n = 1). The affected choroid showed smooth anterior contour (n = 15) and thinned or compressed choriocapillaris (n = 2), thinned (n = 3) or thickened (n = 3) medium vessels, and thinned large vessels (n = 2). The subfoveal choroid was a mean 23% thicker in the involved eye, with a mean thickness of 326.4 µm (median, 326 µm; range, 120-459 µm) compared with 264.4 µm (median, 260 µm; range, 94-462 µm) in the uninvolved eye (P = 0.15). The choroidal perivascular interstitial tissue was 51% thicker in the study eye, enwrapping and silhouetting the medium and large vessels (P = 0.01). The ratio between the perivascular stromal tissue and the subfoveal choroidal thickness was 66% in the study eye and 54% in the normal eye (P = 0.0001). Deep partial (n = 5) or complete (n = 2) tissue shadowing was noted. CONCLUSIONS: Enhanced depth imaging OCT revealed that choroidal melanocytosis shows increased subfoveal choroidal thickness with an apparent increase in the choroidal perivascular stromal tissue and minimal effect on the overlying retina.

Multiple congenital melanocytic nevi and neurocutaneous melanosis are caused by postzygotic mutations in codon 61 of NRAS.

Congenital melanocytic nevi (CMN) can be associated with neurological abnormalities and an increased risk of melanoma. Mutations in NRAS, BRAF, and Tp53 have been described in individual CMN samples; however, their role in the pathogenesis of multiple CMN within the same subject and development of associated features has not been clear. We hypothesized that a single postzygotic mutation in NRAS could be responsible for multiple CMN in the same individual, as well as for melanocytic and nonmelanocytic central nervous system (CNS) lesions. From 15 patients, 55 samples with multiple CMN were sequenced after site-directed mutagenesis and enzymatic digestion of the wild-type allele. Oncogenic missense mutations in codon 61 of NRAS were found in affected neurological and cutaneous tissues of 12 out of 15 patients, but were absent from unaffected tissues and blood, consistent with NRAS mutation mosaicism. In 10 patients, the mutation was consistently c.181C>A, p.Q61K, and in 2 patients c.182A>G, p.Q61R. All 11 non-melanocytic and melanocytic CNS samples from 5 patients were mutation positive, despite NRAS rarely being reported as mutated in CNS tumors. Loss of heterozygosity was associated with the onset of melanoma in two cases, implying a multistep progression to malignancy. These results suggest that single postzygotic NRAS mutations are responsible for multiple CMN and associated neurological lesions in the majority of cases.

[Asymptomatic neonatal neurocutaneous melanosis]. / Mélanose neurocutanée néonatale asymptomatique.

Giant congenital nevi in 1% of cases are associated with anomalies of the central nervous system, which are characteristic of neurocutaneous melanosis. When neurocutaneous melanosis becomes symptomatic, it is associated with a poor prognosis. With recommended neonatal screening, asymptomatic neonatal cases are being discovered more frequently. On the basis of this observation, we consider various aspects of this association.

Neurocutaneous melanosis in association with proliferative skin nodules.

We report the case of a 15-year-old boy with giant congenital melanocytic nevi on his back, buttocks, and rear of the two proximal thirds of his thighs, and neurocutaneous melanosis, diagnosed when he was 3 years old. Three melanocytic nodules were present in the giant nevi that were suspected to have malignant degeneration. A biopsy of these nodules was carried out, and histological study revealed benign proliferative melanocytic nodules within the giant congenital melanocytic nevi.